Stated briefly, our objectives are as follows: a) To investigate changes in drug metabolism associated with the aging process by delineating the relative importance and interrelationships of selected pathways (e.g., dealkylation, hydroxylation, glucuronidation) in older persons taking specific (model) benzodiazepines selected to illuminate each pathway. Younger adults will be studied for comparative purposes. b) To determine blood levels for benzodiazepines in patients receiving emergency room care for benzodiazepine overdosage; to assess the relationship between blood levels and morbidity; and to evaluate the usefulness of these levels for clinical care and treatment planning. c) To continue our studies of drug interactions. d) To reestablish our program of prospective monitoring of drug-induced adverse reactions focusing on haloperidol, a widely used antipsychotic agent. In addition to standard monitoring procedures, we will utilize blood levels and a profile of patient characteristics as possible predictors or determinants of sources of variance in individual differences in susceptibility to unwanted drug effects (e.g., acetylator phenotype; history of migraine headaches, motion sickness; degree of hypochondriasis and amount of recent life stress). e) To investigate the development of tolerance (physiological) to benzodiazepines by studying changing thresholds to amobarbital-induced bilateral gaze nystagmus in subjects taking benzodiazepines for varying amounts of time. f) To continue to improve the practicing clinician's understanding of rational therapeutic approaches by extending our educational efforts in clinical psychopharmacology.